They identify the brain network responsible for Parkinson’s

The brain network that links thought with movement, called SCANwas first described by researchers from WashU Medicine in 2023 and has been identified in a new study as the neurological basis of the disease Parkinson’s. An experimental therapy targeting this network more than doubled symptom improvement in a small group of patients with Parkinson’s, a disease characterized by hyperconnectivity (left side of illustration) between SCAN and the cerebral subcortex.

Parkinson’s disease, a progressive neurological disorder that affects more than one million people in the US now more than ten million worldwideis characterized by debilitating symptoms such as tremors, movement difficulties, sleep disturbances, and cognitive impairment. While current treatments, such as long-term medication and invasive deep brain stimulation (DBS), can relieve symptoms, they cannot stop progression or cure the disease.

A new international study led by the China Changping Laboratoryin collaboration with the Faculty of Medicine of the University of Washington in San Luis and other institutions, identifies the brain region responsible for the core problems of Parkinson’s disease. By targeting this brain network—the somatocognitive action network (SCAN)—with a non-invasive experimental therapy called transcranial magnetic stimulation (TMS), symptom improvement was more than double in a small group of patients, compared to TMS targeting surrounding brain areas.

The study, published on February 4 in Nature, redefines the neurological basis of Parkinson’s and lays the foundation for a more effective and precise treatment of the disease.

“This work demonstrates that Parkinson’s is a SCAN disorder, and the data strongly suggest that by targeting SCAN in a personalized and precise way, Parkinson’s can be treated more successfully than before,” said co-author Nico U. Dosenbach, MD, PhD, David M. & Tracy S. Holtzman Professor of Neurology at WashU Medicine. “Modifying SCAN activity could slow or reverse disease progression, not just treat symptoms.”

Treating the root of Parkinson’s

Dosenbach first described SCAN in Nature in 2023. This network is located in the motor cortex (the part of the brain that controls body movements) and is responsible for converting action plans into movements and receiving feedback on their execution. Since Parkinson’s disease causes a wide range of symptoms that affect bodily functions such as movement, digestion, and sleep, as well as cognition and motivation, the Dr. Hesheng Liulead author of the study, collaborated with Dosenbach to explore whether SCAN dysfunction, which links cognition to movement, could explain Parkinson’s symptoms and serve as a therapeutic target.

Liu’s team collected diverse brain imaging data from more than 800 participants at various institutions in the US and China. The group included patients with Parkinson’s who received deep brain stimulation (ECP), which uses surgically implanted electrodes to send electrical impulses to specific areas of the brain, or non-invasive treatments such as transcranial magnetic stimulation, focused ultrasound stimulation, and medications. Healthy individuals and patients with other movement disorders were also included as controls.

The authors’ analysis revealed that the Parkinson’s is characterized by hyperconnectivity between the SCAN and the subcortexthe part of the brain responsible for emotions, memory, and motor control. The four therapies included in the study were most effective in reducing hyperconnectivity between the SCAN and the subcortex, thus normalizing activity in the circuit responsible for planning and coordinating actions.

“For decades, Parkinson’s has been primarily associated with motor deficits and deficits in the basal ganglia,” the part of the brain that controls muscle movements, Liu said. “Our work shows that the disease has its origin in a dysfunction of the much broader neuronal network. The SCAN is hyperconnected with key regions associated with the disease, and this abnormal wiring alters not only movement, but also related cognitive and bodily functions.”

Taking advantage of this knowledge, the researchers developed a new precision treatment system capable of targeting the SCAN non-invasively with millimeter precision. They applied transcranial magnetic stimulation, which sends magnetic pulses to the brain from a device in the head. In a clinical trial, 18 patients receiving transcranial magnetic stimulation targeting the SCAN showed a response rate of 56% after two weeks, compared to 22% in a group of 18 patients receiving stimulation in adjacent brain areas, representing a 2.5-fold increase in efficacy.

“With non-invasive treatments “We could start treating with neuromodulation much earlier than we currently do with DBS” because they do not require brain surgery, Dosenbach said.

Dosenbach added that more basic research needs to be done to understand whether and how different components of SCAN affect different Parkinson’s symptoms.

Dosenbach is planning clinical trials with Turing Medicala WashU Medicine startup he co-founded, to test a non-invasive treatment that uses surface electrode strips placed over SCAN regions to treat gait dysfunction in Parkinson’s patients. He also plans to investigate modulating SCAN with low-intensity focused ultrasound, a non-invasive way to modify brain activity using acoustic energy.